scholarly journals Bacillus subtilis Spore-Trained Dendritic Cells Enhance the Generation of Memory T Cells via ICAM1

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2267
Author(s):  
Jian Lin ◽  
Lulu Huang ◽  
Yuchen Li ◽  
Penghao Zhang ◽  
Qinghua Yu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Bacillus Subtilis ◽  
Memory T Cells ◽  
Immune Memory ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Entry Site ◽  
Bacillus Subtilis Spore ◽  
Circulating T Cells

Immunological memory is a cardinal feature of the immune system. The intestinal mucosa is the primary exposure and entry site of infectious organisms. For an effective and long-lasting safeguard, a robust immune memory system is required, especially by the mucosal immunity. It is well known that tissue-resident memory T cells (Trms) provide a first response against infections reencountered at mucosal tissues surfaces, where they accelerate pathogen clearance. However, their function in intestinal immunization remains to be investigated. Here, we report enhanced local mucosal and systemic immune responses through oral administration of H9N2 influenza whole inactivated virus (H9N2 WIV) plus Bacillus subtilis spores. Subsequently, H9N2 WIV plus spores led to the generation of CD103+ CD69+ Trms, which were independent of circulating T cells during the immune period. Meanwhile, we also found that Bacillus subtilis spores could stimulate Acrp30 expression in 3T3-L1 adipocytes. Moreover, spore-stimulated adipocyte supernatant also upregulated the expression of intercellular adhesion molecule-1 (ICAM1) in dendritic cells (DCs). Furthermore, the proportion of HA-tetramer+ cells was severely curtailed upon suppressed ICAM1 expression, which also depended on HA-loaded DCs. Taken together, our data demonstrated that spore-promoted H9N2 WIV induced an immune response by enhancing Trms populations, which were associated with the activation of ICAM1 in DCs.

scholarly journals Bacillus subtilis spore induces efficient generation of memory T cells via ICAM-1 expression on dendritic cells

2020 ◽  
Author(s):  
Lulu Huang ◽  
Jian Lin ◽  
Yuchen Li ◽  
Penghao Zhang ◽  
Qinghua Yu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Bacillus Subtilis ◽  
Memory T Cells ◽  
Intercellular Adhesion Molecule ◽  
Subtilis Spore ◽  
Intercellular Adhesion Molecule 1 ◽  
Entry Site ◽  
Bacillus Subtilis Spore ◽  
Resident Memory T Cells

AbstractThe intestinal mucosa is the primary exposure and entry site of infectious organisms. Tissue-resident memory T cells (Trms) is an important first line of defense against infection in mucosal tissues, their function in intestinal immunization remains to be investigated. Here, we reported that the levels of local mucosal and systemic immune responses were enhanced through oral immunization with H9N2 whole inactivated virus (H9N2 WIV) plus spore. Subsequently, H9N2 WIV plus spore led to the generation of CD103+CD69+ Trms, which was independent of circulating T cells during the immune period. Meanwhile, we also found that Bacillus subtilis spore can stimulate Acrp30 expression in 3T3-L1 adipocytes. Moreover, adipocyte supernatant or spore also upregulated intercellular adhesion molecule-1 (ICAM-1) expression on dendritic cells (DCs) (P<0.01). Furthermore, the proportion of HA-tetramer+cells was severely curtailed when ICAM-1 expression was suppressed, which was also dependent on HA-loaded DCs. Taken together, our data demonstrated that spore promoted the immune response by stimulating Trms, which were associated with activation of ICAM-1 in DCs.Author summaryTaken together, Bacillus subtilis spore combined with H9N2 WIV enhanced the mucosal antibody response and induced efficient intestinal-resident memory T cells. Then we demonstrated that spore can induce memory T cell formation through an ICAM-1-mediated contact of a dendritic cell (DC)-derived mechanism. Further, our findings indicated that Acrp30 from adipocytes induced by spore might increase ICAM-1 expression on DCs, which might provide new insight into the significance of adipocyte metabolism related molecules in regulating immunological memory T cells.

scholarly journals Intraepithelial airway dendritic cells: a distinct subset of pulmonary dendritic cells obtained by microdissection.

1992 ◽  
Vol 175 (3) ◽  
pp. 797-807 ◽  
Author(s):  
J L Gong ◽  
K M McCarthy ◽  
J Telford ◽  
T Tamatani ◽  
M Miyasaka ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Intercellular Adhesion Molecule ◽  
Immunoperoxidase Staining ◽  
Intercellular Adhesion Molecule 1 ◽  
Ifn Gamma ◽  
Distinct Subset ◽  
Tracheobronchial Epithelium ◽  
And Function

Dendritic cells (DC), in general, and pulmonary DC, in particular, are a heterogeneous population of cells, their phenotype and function being dependent on their anatomic location, their state of activation, and the regulatory effect of locally secreted cytokines. Using a novel microdissection technique, the epithelium from the trachea and entire airway system was harvested, and the contained DC isolated at greater than 90% purity. The phenotype and function of these airway DC (ADC) was compared to DC isolated, at greater than 90% purity, from the parenchyma of the same lung. In contrast to lung DC (LDC), ADC did not express intercellular adhesion molecule 1 (ICAM-1) in situ, the amount of immune associated antigen (Ia) expressed was less (as determined by immunoperoxidase staining and immunopanning), and greater than 50% of ADC displayed Fc receptors (FcR). The majority of LDC were ICAM-1+, less than 5% expressed FcR, and all were intensely Ia+. Airway DC were most numerous in tracheal epithelium, but they were also present in small numbers in the epithelium of the most distal airways. Their numbers increased in all segments of the tracheobronchial epithelium in response to the administration of IFN-gamma. ADC were consistently more effective than LDC in presenting soluble (hen egg lysozyme) and particulate (heat-killed Listeria monocytogenes) antigens to antigen-sensitized T cells. By contrast, LDC were significantly more efficient in stimulating the proliferation of nonsensitized T cells in an autologous mixed leukocyte reaction. These data suggest that in normal animals, intraepithelial DC of airways share many attributes with Langerhans cells of the skin. Interstitial LDC, by contrast, reside in an environment where they may be exposed to a different set of regulatory factors and where they have progressed to a more advanced stage of differentiation than ADC. Both groups of DC are, however, heterogeneous, reflecting the continuous turnover that these cells undergo in the lung.

scholarly journals The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro.

1994 ◽  
Vol 180 (5) ◽  
pp. 1849-1860 ◽  
Author(s):  
K Inaba ◽  
M Witmer-Pack ◽  
M Inaba ◽  
K S Hathcock ◽  
H Sakuta ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Cell Types ◽  
Intercellular Adhesion Molecule ◽  
Oral Epithelium ◽  
Lymphoid Tissues ◽  
Intercellular Adhesion Molecule 1 ◽  
Short Period

B7-2 is a recently discovered, second ligand for the CTLA-4/CD28, T cell signaling system. Using the GL-1 rat monoclonal antibody (mAb), we monitored expression of B7-2 on mouse leukocytes with an emphasis on dendritic cells. By cytofluorography, little or no B7-2 was detected on most cell types isolated from spleen, thymus, peritoneal cavity, skin, marrow, and blood. However, expression of B7-2 could be upregulated in culture. In the case of epidermal and spleen dendritic cells, which become highly immunostimulatory for T cells during a short period of culture, the upregulation of B7-2 was dramatic and did not require added stimuli. Lipopolysaccharide did not upregulate B7-2 levels on dendritic cells, in contrast to macrophages and B cells. By indirect immunolabeling, the level of staining with GL-1 mAb exceeded that seen with rat mAbs to several other surface molecules including intercellular adhesion molecule 1, B7-1, CD44, and CD45, as well as new hamster mAbs to CD40, CD48, and B7-1/CD80. Of these accessory molecules, B7-2 was a major species that increased in culture, implying a key role for B7-2 in the functional maturation of dendritic cells. B7-2 was the main (&gt; 90%) CTLA-4 ligand on mouse dendritic cells. When we applied GL-1 to tissue sections of a dozen different organs, clear-cut staining with B7-2 antigen was found in many. B7-2 staining was noted on liver Kupffer cells, interstitial cells of heart and lung, and profiles in the submucosa of the esophagus. B7-2 staining was minimal in the kidney and in the nonlymphoid regions of the gut, and was not observed at all in the brain. In the tongue, only rare dendritic cells in the oral epithelium were B7-2+, but reactive cells were scattered about the interstitial spaces of the muscle. In all lymphoid tissues, Gl-1 strongly stained certain distinct regions that are occupied by dendritic cells and by macrophages. For dendritic cells, these include the thymic medulla, splenic periarterial sheaths, and lymph node deep cortex; for macrophages, the B7-2-rich regions included the splenic marginal zone and lymph node subcapsular cortex. Splenic B7-2+ cells were accessible to labeling with GL-1 mAb given intravenously. Dendritic cell stimulation of T cells (DNA synthesis) during the mixed leukocyte reaction was significantly (35-65%) blocked by GL-1.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals 453 Novel combination immunotherapy for boosting and priming immune responses in pancreatic cancer: strong anti-tumour effects with interleukin-15 and CD40 agonist treatment

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A480-A480
Author(s):  
Jonas Van Audenaerde ◽  
Elly Marcq ◽  
Bianca von Scheidt ◽  
Ashleigh Davey ◽  
Amanda Oliver ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Dendritic Cells ◽  
Natural Killer ◽  
Mouse Models ◽  
Cd8 T Cells ◽  
Tumour Growth ◽  
Immune Memory ◽  
Combination Immunotherapy ◽  
Interleukin 15

BackgroundWith the poorest 5-year survival of all cancers, improving treatment for pancreatic cancer is one of the biggest challenges in cancer research. In this era of combination immunotherapies, we sought to explore the potential of combining both priming and activation of the immune system. To achieve this, we combined a CD40 agonist with interleukin-15 and tested its potential in pancreatic cancer.MethodsTwo different mouse models of pancreatic cancer were used to assess the potential of this combination regimen. Therefore, effects on tumour growth kinetics and survival were charted. Differential effects on immune signatures was investigated using RNA sequencing. Functional immune subset involvement was tested using different immune depletion experiments and multicolour flow cytometry in different relevant immune sites. Immune memory was checked using re-challenge experiments.ResultsWe demonstrated profound reduction in tumour growth and increased survival of mice with the majority of mice being cured when both agents were combined, including an unprecedented dose reduction of CD40 agonist without losing any efficacy (fig 1). RNA sequencing analysis showed involvement of natural killer cell and T cell mediated anti-tumour responses and the importance of antigen-presenting cell pathways. This combination resulted in enhanced infiltration of tumours by both cytotoxic T cells and natural killer cells, as well as a striking increase in the ratio of CD8+ T cells over T regulatory cells. We also observed a significant increase in numbers of dendritic cells in tumour draining lymph nodes, particularly CD103+ dendritic cells with cross-presentation potential. A critical role for CD8+ T cells and involvement of natural killer cells in the anti-tumour effect was highlighted. Importantly, strong immune memory was established, with an increase in memory CD8+ T cells only when both interleukin-15 and the CD40 agonist were combined.Abstract 453 Figure 1Tumour kinetics and survival in Panc02 (left) and KPC (right) pancreatic cancer mouse modelsConclusionsWe demonstrated profound synergistic anti-tumour effects upon combination of CD40 agonist and interleukin-15 treatment in mouse models of pancreatic cancer. This preclinical data supports initiation of a first-in-human clinical trial with this combination immunotherapy strategy in pancreatic cancer.

scholarly journals Id3 and Bcl6 Promote the Development of Long-Term Immune Memory Induced by Tuberculosis Subunit Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 126
Author(s):  
Jiangyuan Han ◽  
Yanlin Ma ◽  
Lan Ma ◽  
Daquan Tan ◽  
Hongxia Niu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Subunit Vaccine ◽  
Memory T Cells ◽  
Transcriptional Factors ◽  
Immune Memory ◽  
Proliferative Potential ◽  
Adeno Associated Virus ◽  
Adjuvant Effects

Long-lived memory cell formation and maintenance are usually regulated by cytokines and transcriptional factors. Adjuvant effects of IL-7 have been studied in the vaccines of influenza and other pathogens. However, few studies investigated the adjuvant effects of cytokines and transcriptional factors in prolonging the immune memory induced by a tuberculosis (TB) subunit vaccine. To address this research gap, mice were treated with the Mycobacterium tuberculosis (M. tuberculosis) subunit vaccine Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64<190–198>-Mtb8.4-Rv2626c (LT70), together with adeno-associated virus-mediated IL-7 or lentivirus-mediated transcriptional factor Id3, Bcl6, Bach2, and Blimp1 at 0, 2, and 4 weeks, respectively. Immune responses induced by the vaccine were examined at 25 weeks after last immunization. The results showed that adeno-associated virus-mediated IL-7 allowed the TB subunit vaccine to induce the formation of long-lived memory T cells. Meanwhile, IL-7 increased the expression of Id3, Bcl6, and bach2—the three key transcription factors for the generation of long-lived memory T cells. The adjuvant effects of transcriptional factors, together with TB fusion protein MH/LT70 vaccination, showed that both Bcl6 and Id3 increased the production of antigen-specific antibodies and long-lived memory T cells, characterized by high proliferative potential of antigen-specific CD4+ and CD8+ T cells, and IFN-γ secretion in CD4+ and CD8+ T cells, respectively, after re-exposure to the same antigen. Overall, our study suggests that IL-7 and transcriptional factors Id3 and Bcl6 help the TB subunit vaccine to induce long-term immune memory, which contributes to providing immune protection against M. tuberculosis infection.

Mast cells and T-cell expansion

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2497-2498
Author(s):  
Susumu Nakae ◽  
Keisuke Oboki ◽  
Hirohisa Saito
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Mast Cells ◽  
Cell Expansion ◽  
Memory T Cells ◽  
T Cell Expansion

IgE/antigen-FcϵRI crosslinking promotes antigen internalization and apoptosis in mouse mast cells. Dendritic cells uptake the apoptotic mast cells carrying internalized antigens, and thus can efficiently present the antigens to memory T cells.

Effect of pregnancy specific β1-glycoprotein on the replicative potential of naive T-cells and immune memory T-cells

2021 ◽  
Vol 172 (8) ◽  
pp. 198-204
Author(s):  
V. P. Timganova ◽  
◽  
L. S. Litvinova ◽  
K. A. Yurova ◽  
O. G. Khaziakhmatova ◽  
...  
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Immune Memory ◽  
Naive T Cells ◽  
Naïve T Cells
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